Patients trisomic for chromosome 21 (Down syndrome) are at increased risk for acute leukemia and the leukemic cells of many patients without Down syndrome have a third chromosome 21. Hence, this chromosome appears to be related to leukemia and this relationship may involve sequences on chromosome 21 which are expressed in hematopoietic cells. The overall goals of this research are to isolate differentiated states of hematopoiesis, to discover the basis for their regulated expression, and to determine whether their expression is altered in leukemic cells. Twenty-three clones from a lambda/human chromosome 21 library which appear to show stage-specific expression in T cells have already been identified. The first aim is to isolate other clones that are specific to T cell, B cell or myeloid cell development. Each clone will be regionally mapped to chromosome 21 and its expression measured in several human cell lines including normal and transformed cells (especially cells at different stages in hematopoiesis), hematopoietic cells stimulated to differentiate, and cells trisomic for chromosome 21. In each case where hematopoietic-specific expression is confirmed, the cloned sequence will be used to characterize its transcript, followed by the isolation or construction of a cDNA. The cDNA will help in identifying the gene's function and in defining the completeness of the genomic clone. The cloned genes will be reintroduced by DNA-mediated transfection into cultured human lymphoid cells, into cells which normally express the gene and into cells which do not express the gene. The purpose of such experiments is to learn whether the recombinant carries the regulatory information for its tissue-\or stage-specific expression. (W)